CPUT Digital Knowledgehttp://digitalknowledge.cput.ac.zaThe Digital Knowledge digital repository system captures, stores, indexes, preserves, and distributes digital research material.Mon, 19 Nov 2018 23:52:27 GMT2018-11-19T23:52:27Z5071Plasma non-esterified fatty acids in patients with multiple sclerosishttp://hdl.handle.net/11189/4726Title: Plasma non-esterified fatty acids in patients with multiple sclerosis
Authors: Hon, Gloudina M; Hassan, Mogamat Shafick; van Rensburg, Janse S; Abel, Stefan; Erasmus, Rajiv T; Matsha, Tandi
Abstract: Objective: The purpose of this study was to investigate the levels of non-esterified fatty acids in plasma
from patients with multiple sclerosis and further to correlate these findings with the neurological profile
as measured by the Kurtzke Expanded Disability Status Scale. Methods: Plasma non-esterified fatty
acids and esterified fatty acids from 30 control subjects and 31 patients with multiple sclerosis were
measured by gas chromatography.
Results: Non-esterified fatty acids C18:2n-6, C20:4n-6, C16:1n-7, C18:1n-7, C18:1n-9, C14:0, C16:0
and C18:0 were significantly increased in plasma from patients with multiple sclerosis, P ≤ 0.01, while
esterified ed fatty acid C18:2n-6 was decreased, P = 0.003. Fatty acid PC C16:1n-7 and non-esterified
fatty acids C16:1n-7, C18:1n-7 and C18:1n-9 showed positive and fatty acids C18:1n-9, C20:0, C22:0
and C24:0 showed inverse correlations with the Functional System Scores.
Conclusions: We have identified increased monounsaturated non-esterified fatty acids in plasma from
patients with multiple sclerosis as indicative of a worse disease outcome. Further, the decrease in fatty
acid C18:2n-6, with increases in non-esterified fatty acids C18:2n-6 and C20:4n-6, suggested a role for
these eicosanoid precursor fatty acids in the inflammatory condition experienced by these patients.
Sat, 01 Jan 2011 00:00:00 GMThttp://hdl.handle.net/11189/47262011-01-01T00:00:00ZMonounsaturated fatty acids in blood cell membranes from patients with multiple sclerosis Inflammationhttp://hdl.handle.net/11189/4716Title: Monounsaturated fatty acids in blood cell membranes from patients with multiple sclerosis Inflammation
Authors: Hon, Gloudina Maria; Hassan, Mogamat Shafick; van Rensburg, Susan Janse; Abel, Stefan; Erasmus, Rajiv T; Matsha, Tandi
Abstract: The aim of this study was to investigate whether blood cell membrane monounsaturated fatty acids were associated with inflammation and disease outcome in patients with multiple sclerosis. The fatty acid composition in peripheral blood mononuclear cell and red blood cell membranes from 26 patients and 25 controls were determined by gas chromatography. Results showed positive associations between C-reactive protein and C16:1n-7, C18:1n-7, and C24:1n-9 in membranes from controls only. In general, C18:1n-9 and C20:1n-9 showed inverse correlations, while C16:1n-7 and C18:1n-7 showed positive correlations with disease outcome. Multiple sclerosis has a known inflammatory component. There is scarcity of literature on the role of monounsaturated fatty acids in inflammation, but results from this study suggested an association in healthy subjects between monounsaturated fatty acids and C-reactive protein, even at physiologically low levels. This association was not found in the plasma from patients. Furthermore, the n-9 and n-7 fatty acids played different roles in disease outcome, and therefore warrant inclusion, together with polyunsaturated fatty acids when investigating the inflammatory aspects of the disease.
Sat, 01 Jan 2011 00:00:00 GMThttp://hdl.handle.net/11189/47162011-01-01T00:00:00ZModulation of key lipid raft constituents in primary rat hepatocytes by fumonisin B1 - Implications for cancer promotion in the liverhttp://hdl.handle.net/11189/6421Title: Modulation of key lipid raft constituents in primary rat hepatocytes by fumonisin B1 - Implications for cancer promotion in the liver
Authors: Burger, HM; Abel, Stefan; Gelderblom, Wentzel
Abstract: Fumonisin B1 (FB1), a group 2B natural occurring carcinogenic mycotoxin, modulated lipid and fatty acid (FA) constituents of lipid rafts isolated from primary hepatocytes following exposure to a cytotoxic concentration of FB1 (250 μM). The major effects observed in rafts, included a significant (p < 0.05) increase in raft cholesterol (CHOL) and glycerophospholipid such as phosphatidylethanolamine (PE), whereas sphingomyelin (SM) decreased (p < 0.05). Changes in lipid constituents resulted in the disruption of important membrane fluidity parameters represented as a decreased (p < 0.05) in the phosphatidylcholine (PC)/PE and PC/(PE+SM) ratios and an increase (p < 0.05) in the CHOL/PL (PL=PC+PE) ratio, suggesting the preservation of lipid raft rigidity and integrity. Observed FA changes in the raft PE fraction included a significant (p < 0.05) increase in C18:2ω-6, C20:3ω-6, C20:4ω-6, C22:4ω-6, C22:5ω-3 and C22:6ω-3, with an increase in total ω-6 and ω-3 polyunsaturated fatty acids (PUFAs). Modulation of the FA content in PE, specifically the C20:4ω-6 PC/PE ratio and PUFA levels, together with changes in CHOL and SM are key determinants regulating the integrity and function of lipid rafts. In primary hepatocytes these changes are associated with the inhibition of cell proliferation and induction of apoptosis. A lipogenic mechanism is proposed whereby FB1 modulates lipid rafts and differentially target cell survival indices of normal and preneoplastic hepatocytes during cancer promotion in the liver.
Mon, 01 Jan 2018 00:00:00 GMThttp://hdl.handle.net/11189/64212018-01-01T00:00:00ZInhibition of sphingolipid biosynthesis in rat primary hepatocyte cultures by fumonisin B1 and other structurally related compoundshttp://hdl.handle.net/11189/6114Title: Inhibition of sphingolipid biosynthesis in rat primary hepatocyte cultures by fumonisin B1 and other structurally related compounds
Authors: van der Westhuizen, L; Shephard, GS; Snyman, SD; Abel, Stefan; Swanevelder, S; Gelderblom, Wentzel
Abstract: he fumonisins and toxins produced by Alternaria alternata f. sp. lycopersici (AAL toxins) are structurally related mycotoxins that disrupt sphingolipid biosynthesis by inhibiting the rate-limiting enzyme, ceramide synthase. Rat primary hepatocytes were exposed to fumonisin B1 (FB1), its N-acetyl analogue, FA1, its fully hydrolysed analogue, AP1 and the AAL toxins (TA and TB) at concentrations of 1 μm for 40 hr in culture. The extent to which these compounds disrupt sphingolipid biosynthesis in hepatocytes in vitro was investigated by analysing the sphingosine (So) and sphinganine (Sa) levels by HPLC. The inhibition of ceramide synthase was irreversible as the Sa:So ratio was maximally increased by FB1 after 24 hr of exposure and the subsequent removal of FB1 had no effect on the ratio as compared with the 40-hr incubation period in the presence of FB1. The Sa concentration was significantly (P<0.01) increased in all the cultures treated with the different structurally related compounds, while only AP1 increased the So concentration significantly (P<0.05) above the control. As AP1 was found to be less effective in disrupting sphingolipid biosynthesis it would appear that the tricarballylic (TCA) moiety is required for maximal inhibition of ceramide synthase. The presence of an amino group appears not to be a requisite for activity, since FA1 increased the Sa:So ratio to the same extent as FB1. The AAL toxins TA and TB increased the Sa concentration significantly (P<0.01) above that of FB1 and FA1, while the Sa:So ratios were altered to the same extent. The structural requirements for the induction of cytotoxicity differ from those required for ceramide synthase inhibition as TA and TB were significantly (P<0.05 to P<0.01) less toxic to primary hepatocytes than FB1 at all the concentrations tested.
Thu, 01 Jan 1998 00:00:00 GMThttp://hdl.handle.net/11189/61141998-01-01T00:00:00ZInduction of an altered lipid phenotype by two cancer promoting treatments in rat liverhttp://hdl.handle.net/11189/6431Title: Induction of an altered lipid phenotype by two cancer promoting treatments in rat liver
Authors: Riedel, S; Abel, Stefan; Swanevelder, S; Gelderblom, Wentzel
Abstract: Changes in lipid metabolism have been associated with tumor promotion in rat liver. Similarities and differences of lipid parameters were investigated using the mycotoxin fumonisin B1 (FB1) and the 2-acetylaminofluorene/partial hepatectomy (AAF/PH) treatments as cancer promoters in rat liver. A typical lipid phenotype was observed, including increased membranal phosphatidylethanolamine (PE) and cholesterol content, increased levels of C16:0 and monounsaturated fatty acids in PE and phosphatidylcholine (PC), as well as a decrease in C18:0 and long-chained polyunsaturated fatty acids in the PC fraction. The observed lipid changes, which likely resulted in changes in membrane structure and fluidity, may represent a growth stimulus exerted by the cancer promoters that could provide initiated cells with a selective growth advantage. This study provided insight into complex lipid profiles induced by two different cancer promoting treatments and their potential role in the development of hepatocyte nodules, which can be used to identify targets for the development of chemopreventive strategies against cancer promotion in the liver.
Thu, 01 Jan 2015 00:00:00 GMThttp://hdl.handle.net/11189/64312015-01-01T00:00:00ZDifferential modulation of the lipid metabolism as a model for cellular resistance to fumonisin B1–induced cytotoxic effects in vitrohttp://hdl.handle.net/11189/5776Title: Differential modulation of the lipid metabolism as a model for cellular resistance to fumonisin B1–induced cytotoxic effects in vitro
Authors: Riedel, S; Abel, Stefan; Burger, Hester-Mari; van der Westhuizen, L; Swanevelder, S; Gelderblom, Wentzel
Abstract: Differential sensitivity of primary hepatocytes and Chang cells to the cancer promoter fumonisin B1 (FB1)-induced cytotoxic effects were investigated in relation to changes in membrane lipid distribution. In contrast to primary hepatocytes, Chang cells were resistant to FB1-induced cytotoxic effects. This was associated with a high cholesterol (Chol) and sphingomyelin (SM) and low phosphatidylcholine (PC) content, resulting in a significant (P<0.05) decrease in phosphatidylethanolamine (PE)/PC ratio, increased Chol/total phosphoglyceride (TPG) ratios and low total polyunsaturated fatty acids (PUFA) content in PC and PE, suggesting a more rigid membrane structure. High levels of C18:1 and reduced polyunsaturated fatty acid (PUFA) levels are likely to provide selective resistance to FB1-induced oxidative stress. FB1-associated lipid changes included decreases in SM and Chol, increases in sphinganine (Sa) and PE with the increases in key saturated, monounsaturated, and PUFAs in PE as key role players in the differential responses to FB1-induced cell growth responses in cells.
Fri, 01 Jan 2016 00:00:00 GMThttp://hdl.handle.net/11189/57762016-01-01T00:00:00ZDietary PUFA and cancerhttp://hdl.handle.net/11189/6432Title: Dietary PUFA and cancer
Authors: Abel, Stefan; Riedel, S; Gelderblom, Wentzel
Abstract: The aim of the present paper is to give a brief overview on the role of dietary fat in carcinogenesis and as possible anticancer agents. Dietary fat is an essential nutrient and important source for the essential fatty acids (FA), linoleic and α-linolenic acids, which contribute to proper growth and development. However, dietary fat has been associated with the development of colorectal, breast, prostate, endometrial and ovarian cancers, with the type and quality of fat playing an underlying role. Tumour growth is the disruption of the homoeostatic balance regulating cell differentiation, proliferation and apoptosis and is associated with altered lipid metabolism. Animal cancer models and human cancer biopsy tissue demonstrate that a characteristic lipid profile is associated with the growth and development of neoplastic lesions. This entails alterations in membrane cholesterol, phospholipid and PUFA metabolism. Particularly, alterations in cell membrane FA metabolism involving the n-6 and n-3 PUFA, are associated with changes in membrane structure, function, cellular oxidative status, activity of enzymes and signalling pathways. These events are a driving force in sustaining the altered growth of cancerous lesions and provide unique targets for intervention/cancer modulation. Challenges in utilising FA in cancer modulation exist regarding intake and effect on cell structure and biochemical interactions within the cell in the prevention of cancer development. Therefore, utilising dietary PUFA in a specific n-6:n-3 ratio may be an important chemopreventive tool in altering the growth characteristics of cancer cells.
Wed, 01 Jan 2014 00:00:00 GMThttp://hdl.handle.net/11189/64322014-01-01T00:00:00Z